If we see the immune system as a whole we see it better. The common view is that the immune system is our defence against infections. This is still the default explanation in medical textbooks and websites, and for most people preventing infection is an understandable priority. However a better way to understand and support immunity is to see it as something much wider than that.
The immune system is a vast array of interlinked mechanisms designed to distinguish substances that are normally found in the body from those that should not be there, and then to set these up for removal.
Why the need for this vigilance? The main focus of the immune system is on proteins and their larger fragments (peptides), as well as other complex molecules. These are known as antigens. However these are the same kind of compounds as the messengers and enablers within the body, the lines of communication between our cells, and the way they have of affecting each other. Our healthy functions would be impossible if internal communications were disrupted by agents that should not be there. So our bodies expend huge resources to keep the channels clear.
When we look at where disruptions to our internal communications can come then we can see that infections are only a minor source. There are two constant and major sources of antigens into the bloodstream and circulating fluids:
- Our food. This is obviously made up of foreign materials, and we would suffer great harm for example if food was injected straight into our tissues. We rely on a healthy digestive system to make food safe. Our digestive juices not only sterilise our food and reduce infection from this source, but render large antigenic molecules into small safe building blocks (eg amino acids and simple sugars).
- The internal contents of our own cells. Proteins inside a cell belong just there. Mostly they have no role in the body fluids and often become antigens if they get out. Cells die and are recycled constantly. This is normally done very rigorously so that internal contents are pre-digested before the cell membrane is breached, a process known as apoptosis. Illness or severe tissue damage can disrupt apoptosis and many forms of immune disease are autoimmunity to our own intracellular contents.
The main role of the immune system is to deliver preventive and eliminative measures against antigenic junk from any source. It also provides an intricate fallback to identify, isolate and flag anything that slips through into the body fluids, so that it can be disposed of.
Essentially therefore the immune system regulates our internal environment. It determines our health. It is also individual: my immune system is also as unique as my fingerprint – it has my name on it!
Note: this broader view of immunity is not new. One of the founding French immunologists Dr Pierre Grabar, wrote that the immune system is a complex ‘transport’ system designed to identify and carry antigens out of the body, particularly from the gut and after cell death.
However because of their complexity immune responses can go wrong. Many modern health conditions, especially if they are long term and severe, involve some degree of immune disruption, particularly autoimmunity, when our immune system targets our own tissues. We should understand the immune system as well as possible so as to develop herbal strategies that may help when it goes wrong.
How does the immune system work?
Immune cells, often also termed ‘white blood cells’, are produced from two types of stem cells in the bone marrow (myeloid and lymphoid) and move through the circulation and lymphatic system to reach all body tissues.
The myeloid stem cell is the precursor to ‘innate’ immune cells, or leucocytes. These are further divided in granulocytes(neutrophils, eosinophils, basophils, mast cells), and monocytes (that can develop into macrophages and dendritic cells). Neutrophils are the most numerous granulocytes and patrol the bloodstream. Basophils or ‘mast cells’ are found in tissues and can release inflammatory chemicals like histamine; with eosinophils they are important for host defence against parasites and are also involved in allergic reactions. Granulocytes can ingest pathogens and other foreign material, digesting them inside special compartments called vesicles (which make up the granulation seen in the microscope).
Monocytes also patrol the circulation. When activated by the presence of danger signals they develop into macrophages (‘big eater’ in Greek), which are able to move through the capillary wall into the tissues ingest and degrade bacteria, recycle dead cells, and clear away cellular debris. Dendritic cells also develop from monocytes: they are an important ‘antigen-presenting cell’ responsible for processing large molecules into “readable” fragments (antigens) and presenting them to adaptive B or T cells.
All these innate immune cells are important first-line responders to challenge: their housekeeping functions occur without activation of an immune response. However they are also key to activating adaptive immunity, below.
The lymphoid stem cell in the bone marrow leads to ‘adaptive’ (aka ‘specific’) immune cells or lymphocytes: made up of B cells (or ‘plasma cells’), T cells and Natural killer (NK) cells. These are responsible for mounting responses to specific antigens. The first time an antigen is identified the adaptive response can take some days to respond but on the basis of this encounter B- and T cells produce ‘memory cells’ which can respond quickly to repeat exposures (memory cells are the aim of vaccination). B cells have two major functions: they produce antibodies to neutralize antigens and they also present antigens to T cells. In the case of pathogens like bacteria antibodies coat the surface and initiate neutralization, opsonization, and complement activation. Neutralization prevents the pathogen from binding and infecting host cells. In opsonization, an antibody-bound pathogen serves as a red flag to alert immune cells like neutrophils and macrophages, to engulf and digest the pathogen. Complement is a process using specific proteins as a membrane-attack complex to directly destroy bacteria.
The most common antibodies (‘immunoglobulins’ or Ig) produced by B cells are IgG antibodies but there are also important types of antibody often associated with the gut wall: IgA, IgD and IgM. There are also IgE antibodies most associated with basophils and mast cells: these are designed to target large parasites like amoebae and worms, but are mostly associated in modern times with allergic responses.
T cells have a variety of roles including killing infected cells and activating or recruiting other immune cells. They are divided into two broad categories: CD8+ T cells or CD4+ T cells. CD8+ T cells also are called cytotoxic T cells. They recognize and remove virus-infected cells and cancer cells. The CD4+ T-cells are often called ‘T helper cells’ (subsets are TH1, TH2, TH17) responsible for coordinating immune resposes to bacteria and other pathogens. TH17 cells are named for their ability to produce interleukin 17 (IL-17), a signalling molecule that activates immune and non-immune cells and important for recruiting neutrophils. Regulatory T cells (Tregs) monitor and inhibit the activity of other T cells. They prevent adverse immune activation and maintain ‘tolerance’, the prevention of immune responses against the body’s own cells and antigens.
Natural killer cells are important for recognizing and killing virus-infected or tumour cells by applying safe apoptotic methods (to reduce antigen production in cell death – see above). NK cells can also be retained as memory cells.
There are particular tissues associated with immune cell activity.
The gut. Around 70% of our immune cells are located with a few centimetres of the gut wall! This reflects the point made earlier, that most of the antigenic challenge we face comes from the food we eat. These accumulations of cells and the lymphatic vessels that concentrate them are collectively known as Gut Associated Lymphatic Tissue (GALT).
We are familiar with tonsils and the appendix as lymphatic concentrations at the upper and lower end of the gut. In the lower small intestine and large bowel there are more diffuse concentrations called ‘Peyers patches’ that come in almost direct contact with the gut contents. They are also where large quantities of IgM antibodies are generated.
A healthy gut microbiome is also vital for healthy immunity. Healthy bacteria like Bifidobacteria and Lactobacilli fend off harmful organisms and reduce the absorption of inflammatory metabolites. They increase tolerance to dietary and microbial antigens and induce protective IgA. They can enhance host immunity to viruses and play an important role as gatekeepers into the body.
Lymphatic system: This is a network of vessels containing lymph and lymph nodes. Immune cells are carried through the network and concentrate in lymph nodes. These are communication and activation hubs where immune cells sample information from the body and initiate defensive action. If excessively activated they can become swollen.
Spleen: The spleen located behind the stomach. Although not directly connected to the lymphatic system, it acts as a mobilising centre for immune cells circulating in the bloodstream.
Thymus: This is where T-cells mature.
Levels of engagement
An immune response is generally divided into innate and adaptive immunity. Innate immunity occurs immediately, when circulating innate cells recognize a problem. Adaptive immunity occurs later, as it relies on the coordination and expansion of specific adaptive immune cells. Immune memory follows the adaptive response, when mature adaptive cells, highly specific to the original pathogen, are retained for later use.
Innate Immunity is a quick response that engages neutrophils, eosinophils, basophils, mast cells, monocytes, dendritic cells, and macrophages listed above, each with specialised functions, along with an array of chemical mediators called cytokines. If engaged in a major response they lead to inflammation. Innate immune cells have the ability to recognise broad categories of threatening materials and also are important for activating adaptive immunity.
Cytokines are small proteins with diverse functions. These include interferons that mediate responses to viruses and bacteria, interleukins which modulate inflammation, chemokines which recruit immune cells to sites under attack, and the tumour necrosis factor (TNF) family that stimulates immune-cell proliferation and activation.
Adaptive immune cells are more specialized, with each adaptive B or T cell bearing unique receptors, They generally rely on innate immune cells to identify, process and present them with antigens particularly in the lymph nodes. After B or T cells are activated, they expand rapidly. As the problem resolves, cells stop dividing and are retained in the body as memory cells. The next time this same antigen enters the body, a memory cell is already poised to react quickly. Their secret is the ability to randomly re-engineer their cell wall receptors to potentially be able to recognise anything.
However it is helpful to elaborate this simple division into several levels of engagement with defence. The usefulness is that it also gives us a way in simply to support immunity with herbs and natural self care approaches.
The immune response can be seen as rings of defence. At the outer levels engagement is constant and symptom-free. At the most inner level responses are the most delayed, the most complex and the most fraught with risks. The levels of engagement can therefore be ranked by their healthiness – they are best illustrated.
Our barriers, our skin, digestive juices and microbiome particularly, are our first line of defence, are always active and instantly effective. Keeping these working well is an easy goal and many herbal agents are ideally suited for this role.
If a pathogen or other antigen gets through the barriers the innate immunity mechanisms (see above) cut in over the following few hours. This battle is upfront and direct. The white blood cells and other agents concerned are also relatively accessible to herbal and natural approaches, so again this makes a great target for treatment.
Inflammation, and its systemic equivalent fever, are often seen today as problems (with anti-inflammatories some of the most widely prescribed medicines). However in a whole-body view they start out as the most powerful innate immune mechanisms available. This tier of defence is accompanied by substantial increases in blood flow, heat and white blood cell activity. In this phase the innate system is firing at many times its normal rate and its chances of cleaning up a problem are very much enhanced. Traditional healing methods were often directed at inflammation and fever management and there is much we can learn about applying these to modern needs.
Acquired or specific immunity is at once the most sophisticated part of the immune system, and the one most likely to lead to immune complications. It is also the hardest to manage when it goes wrong: conventional approaches tend towards steroids and other immunosuppressants and the only other way to relieve problems is to reduce challenges to it by removing provocative factors as far as possible.
What can go wrong?
Complications arise when the immune system does not function properly. They can range from allergies through immune deficiency syndromes, to complex auto-immune diseases, dangerous acute sepsis and some cancers.
Allergies (‘hypersensitivity reactions’), occur in response to harmless environmental allergens like pollen or food. Hypersensitivity reactions are divided into four classes. Class I, II, and III are caused by antibodies, IgE or IgG, which are produced by B cells in response to an allergen. Overproduction of these antibodies activates immune cells like basophils and mast cells, which respond by releasing inflammatory chemicals like histamine. Class IV reactions are caused by T cells, which may either directly cause damage themselves or activate macrophages and eosinophils that damage host cells.
Immune deficiencies may be short-term or permanent. Temporary immune deficiency can be caused by anything that weakens the immune system. Common infections, especially viral infections, can suppress the immune system, sometimes for long periods (‘post-viral syndrome). There is a variable suppression in pregnancy. More severe targeting of immune cells can occur after chemotherapy and other immunosuppressive therapy, bone marrow transplants, or in HIV. There are a number of rarer primary immune deficiency diseases.
Breakdown in immune tolerance. Tolerance is the prevention of an immune response against a particular antigen. For instance, the immune system is generally tolerant of self-antigens, so it does not usually attack the body’s own cells, tissues, and organs. Autoreactive cells are screened out in embryonic development, and immunological peace is also maintained by regulatory T cells. The brain and eye are additionally protected from immune attack by tougher blood vessel walls called the blood-brain barrier. When tolerance is lost, disorders like autoimmune disease or food allergy may occur.
Autoimmune diseases occur when self-tolerance is broken. B cells may produce antibodies targeting host cells, and active T cells may recognize self-antigen. This amplifies when they recruit and activate other immune cells. Autoimmunity is either organ-specific or systemic. For instance, type I diabetes is organ-specific and caused by immune cells erroneously recognizing insulin-producing pancreatic β cells as foreign. Psoriasis is an AI disease where the basal layer in the skin is attacked; multiple sclerosis targets the nerve fibres; in Crohn’s and ulcerative colitis the cells lining the gut wall are damaged. In various rheumatoid diseases like rheumatoid arthritis and ankylosing spondylitis the conditions are more systemic, involving other tissues as well as the joints. In systemic lupus erythematosus, commonly called lupus, antibodies recognize antigens expressed by nearly all healthy cells.
Sepsis follows often an infection and is a systemic inflammatory state caused by the uncontrolled release of cytokines (‘cytokine storm’). It has been the major risk of severe infection with Covid-19. The systemic release of cytokines may lead to loss of blood pressure, resulting in septic shock and possible multi-organ failure.
Some forms of cancer are directly caused by the uncontrolled growth of immune cells. Leukemia is cancer caused by white blood cells. Lymphoma is cancer caused by lymphocytes. Myeloma is cancer caused by plasma cells. In addition, there is a wider view is that cancer progression in general may partially result from the ability of cancer cells to avoid immune detection.
By understanding the levels of engagement with immunity outlined above it is clear that the best way to use herbs is in supporting the outer tiers, and as far as possible reduce involvement of adaptive immunity, involving antibodies and T cells.
The strategies can be summarised under the following headings:
Improving surface defences and maintaining gut wall integrity: Herbs have been used since prehistory for wound repair and work particularly well as topical healing agents. They also have a direct effect on mucosal surfaces in the mouth, throat, and down the digestive tract. Herbs with astringent qualities (containing tannins), with high resin levels (such as myrrh, boswelia and calendula) should be considered. Echinacea is largely a mucosal-active remedy (and this undermines the concern that echinacea can boost an immunological disease: it works in a different place!) and elderberry also works primarily in the mouth and throat. The effect of medicinal mushrooms like reishi, maitake and shiitake are likely to be mediated by beta-glucans what act primarily on the gut surface.
Lower down the gut the major surface defence is provided by an intact gut wall. A number of mucilaginous remedies like aloe vera, gum arabic and slippery elm have shown promise in maintaining gut wall integrity. Gotu kola, licorice, and meadowsweet are used by practitioners for this purpose and golden seal is almost a specific (and is also a powerful bitter – see below). Among the resins boswel,lia is likely to be most effective lower down in the gut. Turmeric and its constituent curcumin have also been shown to protect gastrointestinal barrier function against cytokine attack and heat stress.
Supporting digestive performance: The stomach and small intestine are zones where hydrochloric acid and digestive enzymes act as the primary defences against antigen intrusions into the body. They not only sterilize food and drink but also break large antigenic molecules, mainly proteins, into safe nutritional building blocks. There are many traditional remedies that optimise these defences. They include any bitters (‘cooling’ in effect) and the warming aromatic digestives (such as spices). Such strategies are particularly relevant where food has become a direct threat, such as classic food allergies as well as some intolerances.
Improving microbiome health: The gut flora is probably the major, and under-estimated contribution to a healthy immune response. Bacteria have an intimate relationship with the gut wall and a healthy balance is certainly the single most important element in maintaining gut wall integrity above. By contrast ‘dysbiosis’ is associated with higher risk of inflammatory damage to the gut wall, invasion by pathogens and the generation of new antigens.
There are very many strategies for maintaining a healthy microbiome. Probiotics, most often fermented foods or supplements, add new cultures, although they first have to survive the sterilizing environment of the stomach and then compete with resident bacteria for a foothold (they are likely most effective when stomach defences are down and the microbiome is particularly depleted). Prebiotics are a most sustained approach, supporting good bacteria either by providing them with food (e.g. vegetable starches) or more intriguingly by engaging in the ‘cross-talk’ between the microbiome and host: these include all plants rich in polyphenols (including most fruits and vegetables) and notably cocoa and pomegranate. Gum arabic is one of a likely range of mucilaginous remedies with prebiotic activity. Turmeric (again) is a confirmed crosstalk prebiotic and other spices are likely to have such effects. Even more interesting is the postbiotic concept, the likelihood that secondary metabolites after digestion and bile action (see below) have beneficial effect on the gut flora.
Working with liver and bile functions: This is uniquely a herbal approach to managing immunity that has been largely overlooked in modern times. However the liver is a major player in managing immune responses, substantially affecting regulatory T cells, producing anti-inflammatory cytokines, improving internal immunisation to permitted antigens, and generating other stabilising influences. Its product bile is also a very important determinant of digestive and microbiome health. Bile acids are produced to help emulsify fats and improve absorption of thse and fat-soluble nutrients. However it is now known that they are major modulators of many body functions: they act on signalling receptors (eg FXR) that repair the gut wall and reduce inflammation throughout the body (even in the brain). Bile acids are both prebiotic and are the main generators of postbiotic materials and have a significant effect in the microbiome. Bile acids can also be harmful especially after they have been absorbed and recycled back through the liver: they can encourage the wrong sort of gut flora, can increase gut inflammation. The key appears to be maintaining healthy digestive, bowel and liver functions to reduce the prospect of the wrong sort of secondary bile acid metabolism.
This is a very broad area of study and more detail will emerge in coming years. For the time being one can use herbs that improve liver function (artichoke, milk thistle and bupleurum for example) and increase the production/dilution of bile (any bitters, artichoke, turmeric, dandelion root) depending on other pointers.
As seen above, the best approach to managing immunological diseases is to reduce the burden on Natural Killer, B and T cells involved in acquired immune responses. Applying the approaches in the previous section is almost always justified, though these should be adjusted to suit the individual situation.
There are some useful strategic approaches to follow.
Look beyond the symptoms: The immunological damage is often some way away from the origin of the problem. Starting out is to start with a blank sheet of paper and look at the whole story, especially over time.
Find the ‘primary lesions’: Many immunological problems are exaggerated response to an earlier infection, gut dysbiosis or other assault on the body defences. ‘Immunological cross-reactivity’ is what immunologists call an immune confusion between the proteins on a bacteria or other pathogen and the proteins on your body tissues. For example rheumatoid arthritis can follow infection with the bacterium Proteus, ankylosing spondylitis with Klebsiella. Asthma is commonly on the back of earlier lung infections.
Crohn’s and ulcerative colitis with previous food poisoning or dysenteric infections. Is there a history of infections, perhaps in the lungs, gut or urinary tract? If so, go back to the earliest for your best clue. Pneumonia in childhood is far more important than if it occurred last month. If you find evidence of a primary lesion treat that as vigorously as possible: almost all severe infections in the past leave subclinical infections (where the bacteria can be cultured from samples) throughout life.
Focus on the gut: As we have seen this is where there are the most immunological action and digestive performance, environmental exposure and the effect of the microbiome are most relevant. It is also where most herbs have their greatest impact. Stay in the gut if in doubt!
Review dietary inputs: Although not as commonly at fault as some suggest, there are genuine reasons for checking whether certain foodstuffs may be exacerbating an immunological problem. Occasionally there are classic food allergies. Here the body accommodates to an early food breach of defences – e.g. in infancy when digestive defences are not sophisticated – with a long-term immunological reaction to that food In the ‘masked food allergy’ version this interaction is covered up with a cocktail of mood-enhancing and immunosuppressive adrenal hormones. In this case the food becomes associated with a lift in mood in spite of the battle going on. The most common culprits are dairy products and gluten but other foods can be involved. The only reliable way to check this is by rigorous elimination diets, cutting out the suspect food absolutely and in all dietary forms for two weeks and then re-challenging.
If the suspect food is firing up an underlying immune response there may be quick changes, starting with withdrawal symptoms in the first few days. Almost as revealing is what happens when the suspect food is introduced: there can be an ‘uncovered up’ reaction to it. One way to check is to take the pulse before and in the 20 minutes after the introduction (‘challenge’): if there is a reaction, it will show with a substantial rise in pulse rate. There are other possible dietary factors. Gluten has been associated with exacerbating Crohn’s disease and a gluten-free diet is worth trying for a few months to see if there is a change in symptoms. In all cases test a hunch rigorously and for a defined time, rather than follow an idea blindly: cutting out foods unnecessarily is likely to do more harm than good.
Take one step at a time: The implication of the ideas above is that a complex immunological condition is best tackled by checking out underlying causes rather than targeting the symptoms – as is the case in conventional treatment. So as well as short-term relief, often involving a doctor’s prescriptions, start working on any causes and check with changes there. It could be a change in digestion or bowel activity, improved lung or urinary functions or circulation, whichever applies. Stick with these stepwise changes so that they can feed through to the main problem in time. There is the real prospect that changes will then be long term.